Normal and rabbit antibodies to antihemophilic factor (AHF, factor VIII) have been used in recent immunologic studies of this central coagulation protein. This project seeks detailed information about the properties of anti-AHF and the way in which they inactivate AHF procoagulant activity. Comparative studies of binding affinity and specificity of human and rabbit anti-AHF will provide important information about these immunologic interactions. Specific attention will be directed toward an understanding of the absence of precipitating antibodies in high titer human anti-AHF sera. Experiments will be carried out using IgG and Fab from rabbit and human sera which have anti-AHF and purified radiolabeled and anti-AHF will be prepared. An understanding of the properties of anti-AHF will permit more effective approaches to prevention and treatment of these antibodies. A more detailed understanding of the immunologic properties of AHF has additional potential value in the continuing study of AHF-deficiency diseases (hemophilia A and von Willebrand's disease). Human anti-AHF will also be used in studies which seek evidence of molecular (immunologic) heterogeneity in normal plasma AHF. A group of antibodies to AHF will be used in experiments which compare inactivation titers for a panel of normal human plasmas. Evidence of heterogeneity in normal human AHF would support present concepts of the basis of antibody formation in transfused hemophilic patients and in postpartum women.